Project Summary Abstract This renewal application (RFA-HD-18-011) is for support of the Child Health Research Center (CHRC) at Washington University School of Medicine. Pediatric physician-scientists play a crucial role in advancing knowledge that improves child health. To meet the ongoing national need to replenish the pediatric physician-scientist pipeline at the junior faculty level, our program supports a mentored career development pathway for 3 Scholars per year for 2-3 years by leveraging a wealth of biomedical resources within the Washington University School of Medicine and the Medical Center campus. As we have done for the past 22 years, the long-term objective of our Center is to develop Scholars that focus their research efforts on Pediatric disease-oriented biology by applying recent advances in the basic sciences, such as developmental biology, cell biology, immunology, genetics/genomics, and systems biology. The specific aims of this proposal include: 1) protected mentored research experiences with well-established investigators encompassing a wide range of disciplines within the Washington University School of Medicine and the Department of Pediatrics, 2) obligatory educational programs in laboratory management, scientific rigor, statistics, grantsmanship and responsible conduct of research, 3) individualized specific coursework based on the Scholars? areas of investigation (e.g., bioinformatics, live-cell imaging), 4) continuous feedback to the Scholars, mentors and CHRC leadership, and 5) foster the development of Scholars who are women and underrepresented minorities. The program, now twenty-two years old, has a stellar track record by exceeding national benchmarks (?K12 to K08/23? conversion rate of 63% and an outstanding ?K to R conversion? rate of 59%; national average <40%, respectively), and will ultimately close the knowledge gap between basic scientists and pediatric clinicians. Gary A. Silverman, M.D., Ph.D. will serve as Program Director, and David Hunstad, M.D. will serve as Training Director. The CHRC and its Scholars will continue to utilize our institutionally-funded state-of-art core facilities that provide, for example, whole genome/exome DNA sequencing, bioinformatics, cryo-EM imaging, genome editing and model animal development, to facilitate the study of Pediatric disease states. The long-term goals of the CHRC are being realized as its Scholars contribute to our understanding of human developmental diseases for decades to come, while evolving into the next generation of scientific leaders, role models and mentors for subsequent generations of Pediatric Scholars.